Bacteria regulate intestinal epithelial cell differentiation factors both in vitro and in vivo.
Bacteria regulate intestinal epithelial cell differentiation factors both in vitro and in vivo.
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DOI：
10.1371/journal.pone.0055620
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Gersemann M
中科院分区：
文献类型：
--
作者：
Becker S;Oelschlaeger TA;Wullaert A;Vlantis K;Pasparakis M;Wehkamp J;Stange EF;Gersemann M
人类结肠中存在大量的细菌，已知这些细菌广泛影响粘膜代谢和功能，并被认为参与炎症性肠病的发病机制和结肠癌的发展。在这份报告中，我们研究了结肠细菌对上皮细胞分化因子的影响，在体外和体内。作为关键的转录因子，我们专注于Hes 1，已知直接朝向吸收细胞的命运，Hath 1和KLF 4，它们控制杯状细胞。用实时荧光定量PCR方法检测LS 174 T细胞中转录因子Hes 1、Hath 1和KLF 4、粘蛋白Muc 1和Muc 2以及防御素HBD 2的表达。大肠杆菌菌株，包括益生菌E.大肠杆菌Nissle 1917+/−鞭毛蛋白、乳酸杆菌和双歧杆菌。对于蛋白质检测，进行蛋白质印迹实验和室载玻片免疫染色。最后，在无菌小鼠、无特定病原体小鼠和常规小鼠的结肠中评价这些因子的mRNA和蛋白质表达，并对结肠杯状细胞进行计数。Hes 1和Hath 1的表达被E. coli K-12和E. coliNissle 1917年。与此相反，Muc 1和HBD 2的表达显着增强，独立的Notch信号通路。益生菌E. coli Nissle 1917通过鞭毛蛋白调控Hes 1、Hath 1、Muc 1和HBD 2。体内实验证实了所观察到的细菌的体外作用，与无菌小鼠相比，无特定病原体和常规小鼠中Hath 1和KLF 4的结肠表达减少，而这些小鼠中杯状细胞的数量不变。肠道细菌影响肠上皮细胞分化因子Hes 1、Hath 1和KLF 4以及Mu 1和HBD 2，在体外和体内。Muc 1和HBD 2的诱导似乎直接由细菌而不是Notch触发。
The human colon harbours a plethora of bacteria known to broadly impact on mucosal metabolism and function and thought to be involved in inflammatory bowel disease pathogenesis and colon cancer development. In this report, we investigated the effect of colonic bacteria on epithelial cell differentiation factors in vitro and in vivo. As key transcription factors we focused on Hes1, known to direct towards an absorptive cell fate, Hath1 and KLF4, which govern goblet cell. Expression of the transcription factors Hes1, Hath1 and KLF4, the mucins Muc1 and Muc2 and the defensin HBD2 were measured by real-time PCR in LS174T cells following incubation with several heat-inactivated E. coli strains, including the probiotic E. coli Nissle 1917+/− flagellin, Lactobacilli and Bifidobacteria. For protein detection Western blot experiments and chamber-slide immunostaining were performed. Finally, mRNA and protein expression of these factors was evaluated in the colon of germfree vs. specific pathogen free vs. conventionalized mice and colonic goblet cells were counted. Expression of Hes1 and Hath1, and to a minor degree also of KLF4, was reduced by E. coli K-12 and E. coli Nissle 1917. In contrast, Muc1 and HBD2 expression were significantly enhanced, independent of the Notch signalling pathway. Probiotic E. coli Nissle 1917 regulated Hes1, Hath1, Muc1 and HBD2 through flagellin. In vivo experiments confirmed the observed in vitro effects of bacteria by a diminished colonic expression of Hath1 and KLF4 in specific pathogen free and conventionalized mice as compared to germ free mice whereas the number of goblet cells was unchanged in these mice. Intestinal bacteria influence the intestinal epithelial differentiation factors Hes1, Hath1 and KLF4, as well as Muc1 and HBD2, in vitro and in vivo. The induction of Muc1 and HBD2 seems to be triggered directly by bacteria and not by Notch.
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影响因子：
4.7
作者：
Biarc, J;Nguyen, IS;Schöller-Guinard, M
通讯作者：
Schöller-Guinard, M
影响因子：
56.9
作者：
Gill, Steven R.;Pop, Mihai;Nelson, Karen E.
通讯作者：
Nelson, Karen E.
影响因子：
3.8
作者：
Abdulamir AS;Hafidh RR;Mahdi LK;Al-jeboori T;Abubaker F
通讯作者：
Abubaker F
影响因子：
29.4
作者：
Cover TL;Blaser MJ
通讯作者：
Blaser MJ
影响因子：
4.4
作者：
Kapoor, Nisha;Narayana, Yeddula;Balaji, Kithiganahalli N.
通讯作者：
Balaji, Kithiganahalli N.